The global incidence, morbidity, and mortality of sexually transmitted diseases (STDs) caused by HIV, HSV, and other viral and microbial pathogens is estimated at several hundred millions individuals worldwide. One approach for the control the transmission of STDs is the use of topically applied, female/male-controlled vaginal, or rectal microbicides that inactivate the relevant pathogens. Consequently, the development of new, safe, topical microbicides for intravaginal or intrarectal use for the prevention and treatment of STDs is an important target for novel drug development.
International Patent Application Nos. PCT/AU95/00350 (WO 95/34595) and PCT/AU99/00763 (WO 00/15240), the contents of which are incorporated herein by reference, disclose a new class of polyvalent agents—the dendrimers, highly branched macromolecules with a definite envelope of polyanionic or cationic surface groups, which have been shown to exhibit a range of antiviral and antimicrobial activity with minimal toxicity. Unlike small molecular structures of most antivirals, these dendrimers are a class of polyvalent, highly branched macromolecular compounds formed by iterative reaction sequences starting from an initial core molecule with successive layers or stages being added in successive “generations” to build up a three-dimensional, highly ordered polymeric compound. Dendrimers are characterised by the following features: i. an initiator core which may have one or more reactive sites and be point-like or of significant size so as to effect the final topology of the dendrimer; ii. layers of branched repeating units attached to the initiator core; iii. functional terminal groups (such as anionic- or cationic-containing moieties) attached to the surface of the dendrimer, optionally through linking groups.
These macromolecular compounds are synthesised from monomeric building blocks with multiple branches or tree-like structures, and the outside surface of the molecule carries a number of functional groups that lead to recognition by a biological receptor.
The preparation of dendrimers is well known, and is described by way of example in U.S. Pat. Nos. 4,289,872 and 4,410,688 (describing dendrimers based on layers of lysine units), as well as U.S. Pat. Nos. 4,507,466, 4,558,120, 4,568,737 and 4,587,329 (describing dendrimers based on other units including polyamidoamine or PAMAM dendrimers).
In antiviral and antimicrobial testing, a subset of these dendrimer structures have unexpectedly shown exceptional activity against a broad spectrum of microorganisms associated with sexually transmitted diseases, that makes them agents of choice for the development of a vaginal or rectal microbicide for the prophylaxis and treatment of sexually transmitted diseases.